The bactericidal capacity of the human neutrophil, the first line of microbicidal defense, is dependent on the cell's ability to generate the respiratory burst, in which a marked increase in oxygen consumption by the activated cell results in the formation of several highly reactive and potentially lethal free radicals. These metabolites of oxygen, superoxide and hydroxyl radical, are not only of potential damage to invading pathogens, but also to host tissue and to the cell responsible for their production. We have recently begun to isolate the respiratory burst enzyme, and have partially characterized its biochemical and physical properties, as well as determined its sub-cellular distribution. The finding that the oxidase is initially "hidden" from the exterior layer of the plasma membrane, and that it is not inhibitable until the cell is activated, suggests new insights into the activation phenomenon of this respiratory burst apparatus. The nature of the specific activation of this respiratory burst oxidase has also been studied to determine the specific requirements for the production of superoxide. The new findings that the oxidase activity is activated by phagocytosis but that superoxide is not necessarily produced, is of potential importance in determining natural bactericidal mechanisms; the capacity of specific bacteria to initiate superoxide production is being studied to determine if pathogenicity is related to this function. The dual investigation of the requirements for superoxide generation and the biochemical properties of the oxidase responsible for its production are leading to the elucidation of an important mechanism of inflammation.